Enhanced Contractile Response of the Basilar Artery to Platelet-Derived Growth Factor in Subarachnoid Hemorrhage
Enhanced Contractile Response of the Basilar Artery to Platelet-Derived Growth Factor in Subarachnoid Hemorrhage
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DOI：
10.1161/strokeaha.108.530196
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发表时间：
2009-02-01
期刊：
影响因子：
8.3
通讯作者：
Kanaide, Hideo
中科院分区：
文献类型：
--
作者：
Maeda, Yoshihisa;Hirano, Katsuya;Kanaide, Hideo
背景和目的：蛛网膜下腔出血(SAH)患者脑脊液中血小板衍生生长因子(PDGF)水平升高。因此，在蛛网膜下腔出血中观察PDGF对基底动脉的收缩作用。方法和结果：采用兔二次失血性蛛网膜下腔出血模型。在对照基底动脉的中层，PDGF在1nmol/L时无收缩作用，而在3nmol/L时可引起轻度收缩。在蛛网膜下腔出血时，PDGF在1nmol/L或更高浓度时可引起[Ca~(2+)]~(2+)升高。1nmol/L PDGF诱导的[Ca~(2+)](I)和张力分别是118 mmol/L K+去极化组的17%和20%。无细胞外Ca~(2+)时，PDGF引起的[Ca~(2+)](I)升高和SAH的收缩作用被取消。在α-毒素通透性蛛网膜下腔出血动物条上，血小板衍生生长因子在300nmol/L钙离子引起的收缩过程中不引起进一步的张力发展，提示对肌丝钙离子敏感性没有直接影响。金雀异黄素10mU/L可完全抑制1nmol/L诱导的血管张力。1nmol/L组大鼠基底动脉肌球蛋白轻链磷酸化水平显著升高。结论：蛛网膜下腔出血时，基底动脉对PDGF的收缩反应增强。PDGF诱导的收缩主要依赖于酪氨酸磷酸化和钙依赖的肌球蛋白轻链磷酸化。因此，对PDGF的反应性增强可能参与了SAH后脑血管痉挛的发生。(笔划。2009年；40：591-596。)
Background and Purpose-The level of platelet-derived growth factor (PDGF) in cerebrospinal fluid is elevated in subarachnoid hemorrhage (SAH). Therefore, the contractile effect of PDGF on the basilar artery was examined in SAH.Methods and Results-A rabbit double-hemorrhage SAH model was used. In the medial layers of the control basilar artery, PDGF had no effect on contraction up to 1 nmol/L, whereas 3 nmol/L PDGF induced slight contraction. In SAH, PDGF induced an enhanced contraction with an increase in [Ca2+](i) at 1 nmol/L and higher concentrations. The levels of [Ca2+](i) and tension induced by 1 nmol/L PDGF in SAH were 17% and 20%, respectively, of those obtained with 118 mmol/L K+ depolarization. The PDGF-induced elevation of [Ca2+](i) and contraction seen in SAH were abolished in the absence of extracellular Ca2+. In alpha-toxin-permeabilized strips of SAH animals, PDGF induced no further development of tension during contraction induced by 300 nmol/L Ca2+, suggesting no direct effect on myofilament Ca2+ sensitivity. Genistein at 10 mu mol/L completely inhibited the tension induced by 1 nmol/L PDGF. The level of myosin light-chain phosphorylation was significantly increased by 1 nmol/L PDGF.Conclusions-These results show that the contractile response to PDGF of the basilar artery was enhanced in SAH. The PDGF-induced contraction depended mostly on tyrosine phosphorylation and Ca2+-dependent myosin light-chain phosphorylation. The enhancement of the responsiveness to PDGF may therefore contribute to the development of cerebral vasospasm after SAH. (Stroke. 2009;40:591-596.)